Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatoma cells were infected with replication-incompetent murine retroviruses containing the selectable gene for amino-3'-glycosyl phosphotransferase (neo) and/or the nonselectable gene for bovine growth hormone (bGH). Expression of these genes was controlled by the promoter regulatory region of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) from the rat, which contains hormone and tissue-specific regulatory elements. Expression of the transduced PEPCK-neo gene was stimulated by Bt2cAMP and glucocorticoids and inhibited by insulin. The amount of RNA which initiated within the retroviral 5' long terminal repeat (5' LTR) was inhibited when internal promoters were present in the retroviral vector. When no internal promoter was present, expression from the 5' LTR was higher and stimulated by glucocorticoids, due to the presence of a glucocorticoid regulatory element in the 5' LTR. Infection of cells with retroviruses altered the basal expression and hormonal regulation of the endogenous PEPCK gene, but had no effect on the expression of the tyrosine aminotransferase gene, which is regulated in a similar manner by cAMP and glucocorticoids. A segment of the PEPCK promoter acted as a hormonally regulated enhancer, bringing the SV40 early promoter under the control of Bt2cAMP. A second, nonselectable gene (PEPCK-bGH), contained in the retroviral vector together with PEPCK-neo, was expressed and regulated appropriately when introduced into hepatoma cells. The proviruses were initially integrated randomly into the host cell genome, but after prolonged selection for expression of the transduced PEPCK-neo gene, cells were selected which contain a predominant site(s) of integration. Among populations of cells, however, the predominant site(s) of proviral integration was different. The selection of cells with a specific site of integration from a population was accelerated by the presence of PEPCK promoter sequences in the provirus. Despite the need to better characterize their effects on the host cell, retroviruses appear to be versatile tools for the specific introduction of regulated genes into cells.
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PMID:Hormonal regulation of chimeric genes containing the phosphoenolpyruvate carboxykinase promoter regulatory region in hepatoma cells infected by murine retroviruses. 284 79

The antagonism by 3 synthetic steroids of the induction of tyrosine aminotransferase and tryptophan dioxygenase by dexamethasone were compared in HTC and FAZA hepatoma cells and in isolated liver cells. It was observed: (i) the sensitivity of liver cells to glucocorticoid agonists and antagonists changed in relation to time of culture; (ii) the extent of the inhibitory effect on enzyme induction depends on the nature of the antagonist; (iii) hepatoma cells, especially HTC cells, appeared more sensitive to glucocorticoid antagonism than liver cells.
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PMID:Effect of potent antiglucocorticoids on dexamethasone induced enzymes in cultured hepatoma and rat liver cells. 286 90

The mechanisms of reversible decrease of hormone-dependent induction of tyrosine aminotransferase (TAT) by rat liver cells after prolonged administration of the glucocorticoid was studied. It was shown that the main links of the glucocorticoid action mechanism (i.e., the formation of a cytoplasmic hormone-receptor complex and the hormone accumulation in the nuclei) do not change under these conditions. It was found also that one of the necessary prerequisites for the decrease of the hormone-dependent induction of TAT is the constant production by liver cells of large amounts of TAT irrespective of whether this process is induced by the glucocorticoid or by a non-hormonal inducer, e.g., tryptophan. Using the dot-hybridization technique, it was demonstrated that the inhibition of hormone-dependent induction of TAT is correlated with the reduction of mRNA TAT. It was supposed that the main links in the mechanism of inhibition of the hormone-dependent induction are the formation of a large excess of the inducible protein--TAT--in the cells as well as the accumulation of end products of the TAT-catalyzed transamination reaction which cause a feed-back repression of the de novo synthesis of TAT. Studies with cell cultures of Morris hepatoma which is known to be sensitive to glucocorticoids revealed the ability of glucose, the end product of gluconeogenesis reactions, to provide for selective inhibition of the hormone-induced accumulation of mRNA TAT in hepatoma cells.
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PMID:[Autogenic regulation of the sensitivity of liver cells to glucocorticoids during prolonged hormonal stimulation]. 289 28

In this study, we examined the activity of recombinant interferon (IFN)-gamma against Plasmodium berghei exoerythrocytic forms (EEF) grown in vitro within the highly differentiated human hepatoma cell line HEPG2. We assayed the effect of IFN-gamma on parasite growth by DNA hybridization using a P. berghei specific DNA probe. The specific activity of IFN-gamma against EEF is very high, and depends upon the time of lymphokine addition. When IFN-gamma is added to HEPG2 cells containing intracellular EEF, 6 hr after sporozoite invasion, parasite DNA replication is inhibited by approximately 75% at 10(3) U/ml and 50% at 1 U/ml. This treatment can either abolish or greatly reduce the infectivity of EEF for mice. When added earlier, 3 hr after completion of sporozoite invasion, IFN-gamma inhibits parasite replication to an even greater degree. The highest levels of inhibition were obtained when IFN-gamma was added 6 hr prior to sporozoite invasion (100% inhibition at 10(2) U/ml, approximately 55% inhibition at 0.1 U/ml, and 17% inhibition at 0.001 U/ml). We found that HEPG2 cells express approximately 44,000 surface receptors for IFN-gamma. These data are consistent with the view that IFN-gamma exerts its antimalarial activity by binding to surface receptors on hepatocytes and inducing intracellular changes unfavorable for parasite development. Tryptophan starvation does not appear to be involved in this process. These findings also support the idea that IFN-gamma, released from immune T cells upon encountering sporozoite antigen, may be an important effector mechanism in sterile immunity to sporozoite challenge.
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PMID:Interferon-gamma inhibits the intrahepatocytic development of malaria parasites in vitro. 295 45

The presence and location of cytochrome P-450 in Donryu rat hepatocyte culture lines, Ac2F cells and 3 other cell lines were assessed by indirect immunofluorescence examination using anti-cytochrome P-450 monoclonal antibodies. Ac2F cells and other hepatocyte cell lines were selectively stained at their nuclear envelope, but not the cytoplasm, with a monoclonal antibody selective to a high-spin form of cytochrome P-448 (P-448H), although this monoclonal antibody stained primary cultured normal rat hepatocytes at both cellular components and did not stain hepatoma cells of 2 transplantation lines. The results of unscheduled DNA synthesis assay with Ac2F cells using several carcinogenic aromatic amines (4-aminoazobenzene derivatives and amino acid pyrolysis products) suggested that this nuclear envelope-associated cytochrome P-450 activates a restricted portion of these aromatic amines, i.e., a tryptophan pyrolysis component and a glutamic acid pyrolysis component. These results indicate that rat hepatocyte culture lines lack (or contain a reduced amount of) the cytoplasmic cytochrome P-450 but maintain a characteristic type of cytochrome P-450, probably a kind of cytochrome P-448H in their nuclear envelope, and this may be involved in oxidative metabolism of a restricted portion of aromatic amines.
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PMID:Immunochemically detected nuclear envelope-associated cytochrome P-450 component(s) in rat hepatocyte culture lines. 311 63

Deprivation of cultured H4 rat hepatoma cells for an essential amino acid (leucine, methionine, tryptophan or phenylalanine) under conditions in which the cells remain highly viable leads to a decrease in cytoplasmic albumin mRNA. The magnitude of this decrease is greatest in tryptophan-deprived and phenylalanine-deprived cells. In the tryptophan-deprived cells there is approximately a 15-17-fold decrease in albumin mRNA relative to total cytoplasmic RNA, and a 7-8-fold specific decrease in albumin mRNA relative to alpha-tubulin mRNA. Deprivation of the H4 cells for leucine or tryptophan causes approximately a 40-45% decrease in albumin gene transcription; however, this effect does not account for the 15-17-fold decrease in albumin mRNA abundancy caused by tryptophan limitation, or the greater effect of tryptophan limitation as compared to leucine limitation on albumin mRNA. Therefore, the decrease in albumin mRNA caused by tryptophan limitation is caused primarily by a post-transcriptional regulatory mechanism.
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PMID:Regulation of albumin mRNA in H4 rat hepatoma cells by the availability of essential amino acids. 317 36

The human P450IIE1 gene, coding for an ethanol-inducible nitrosamine-metabolizing P-450, was isolated from a lambda EMBL3 genomic library and completely sequenced. The human gene spanned 11,413 base pairs and contained nine exons and a typical TATA box. Upstream and downstream DNAs of 2788 and 559 base pairs were also sequenced and compared to the rat gene. Significant areas of sequence similarity were observed within 140 base pairs upstream of the transcription start site in the rat and human genes. Human DNA 539 base pairs upstream of the transcription start site was inserted into the expression vector pSVOAL delta 5', and luciferase activity was detected when the constructs were introduced into a rat hepatoma cell line. The activity was over 100-fold lower than that of pRSVL, a Rous sarcoma virus LTR-driven luciferase gene. By use of panels of rodent-human cell hybrids, the gene was mapped to chromosome 10 (CYP2E locus). A full-length cDNA, constructed with the first exon of the genomic clone and a partial cDNA clone, was expressed in COS cells and found to code for N-nitrosodimethylamine demethylase activity.
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PMID:Human ethanol-inducible P450IIE1: complete gene sequence, promoter characterization, chromosome mapping, and cDNA-directed expression. 323 19

Immunocytochemical staining of tryptophan 2, 3-dioxygenase (TO, EC 1.13.11.11), which is a typical marker of terminal differentiation of rat hepatocytes, showed that TO was expressed as early as the first day after birth by a few hepatocytes, and that the number of hepatocytes expressing TO gradually increased during early neonatal development. In contrast, immature hepatocytes grew actively in culture even without growth factors and serum, showing a labelling index with [3H]thymidine of over 80% just after birth, but their ability to show autonomous growth decreased rapidly during postnatal development. Double staining of hepatocytes from neonatal rats indicated that hepatocytes showing DNA synthesis were distinct from those expressing TO, suggesting that immature cells proliferate, but do not express TO, and then become fully differentiated expressing TO, but not proliferating any more. On the contrary, albumin was fully expressed in most hepatocytes of 0-day-old rats, in which the hepatocytes were still growing. When immature hepatocytes without TO from 0-day-old rats were cultured on a feeder layer of adult rat hepatocytes for 3.5 days, their expression of TO increased rapidly to almost the adult level (over 70% of the cells became TO-positive). Conversely, this feeder layer strongly inhibited autonomous growth of the neonatal rat hepatocytes. Other feeder layers, such as non-parenchymal liver cells of adult rats, Reuber hepatoma, and Swiss 3T3 fibroblasts, had no effect on the reciprocal changes of terminal differentiation and autonomous growth of immature rat hepatocytes. A feeder layer of dead adult rat hepatocytes, obtained by treating the cells with cytosine arabinoside for 24 h or drying them at 37 degrees C, had the same ability as a feeder layer of living cells to induce cytodifferentiation of immature cells. When the dead feeder layer was treated with 1 N HCl or digested with 0.1% trypsin, its ability to induce differentiation was almost completely lost. These results suggest that a cell surface component of adult rat hepatocytes, probably an acid-labile protein, controls terminal differentiation and growth of immature hepatocytes.
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PMID:In vitro induction of terminal differentiation of neonatal rat hepatocytes by direct contact with adult rat hepatocytes [corrected]. 348 31

The non-specific lipid transfer protein (nsL-TP) purified from rat and bovine liver accelerates the transfer of all common diacylglycerophospholipids, cholesterol as well as glycosphingolipids and gangliosides between membranes. These proteins have molecular weights in the order of 14 500 and are highly basic (isoelectric points between 8.5 and 9.5). The primary structure of nsL-TP from bovine liver has been elucidated yielding a single polypeptide chain of 121 aminoacid residues. The protein contains one cysteine residue, essential for transfer activity, a single tryptophan residue and lacks histidine, arginine and tyrosine residues. Rat liver nsL-TP was found to be identical to sterol carrier protein 2, stimulating the microsomal conversion of intermediates between lanosterol and cholesterol. Evidence was presented that nsL-TP binds cholesterol, suggesting that it acts as a carrier. On the other hand, failure to bind phospholipids disagrees with this proposed mode of action. A sensitive enzyme immunoassay was developed to determine levels of nsL-TP in rat tissues. By use of this assay, nsL-TP was found to be most prominently present in liver and intestinal mucosa (0.78 and 0.46 microgram nsL-TP per mg protein in 105 000 X g supernatant, respectively). Subfractionation studies showed that approx. 70% of nsL-TP was present in the membrane-free cytosol. However, application of an immunosorbent-purified antibody and protein A-linked gold particles to rat liver slices demonstrated a concentration of label over the peroxisomes. By way of immunoblotting it was shown that nsL-TP was absent from peroxisomes and that the immunoreactive material was a protein of mol. wt. 58 000. nsL-TP is capable of mediating net transfer of cholesterol to membranes, deficient in this lipid. Under such conditions of net transfer, nsL-TP stimulated the microsomal esterification of cholesterol and its conversion to pregnenolone by adrenal mitochondria. Levels of nsL-TP in Reuber H35 hepatoma cells was six per cent of that found in rat hepatocytes. This very low level of nsL-TP had no effect on de novo cholesterol biosynthesis and intracellular cholesterol esterification. These results raise doubts as to whether nsL-TP has a function in in situ cholesterol metabolism.
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PMID:The non-specific lipid transfer protein (sterol carrier protein 2) from rat and bovine liver. 406 21

-A comparison of the elution profiles of 18 aminoacyl-tRNA's from Novikoff hepatoma with those from normal liver on a methylated albuminkieselguhr column revealed the occurrence of new species of tRNA for histidine, tyrosine, and asparagine in the hepatoma. In addition, the hepatoma tRNA's for arginine, isoleucine, lysine, methionine, serine, alanine, and tryptophan eluted at a higher salt concentration than the corresponding tRNA's of normal liver. The remaining eight amino acids did not show any significant differences in the elution profiles.
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PMID:Differences in the transfer RNA's of normal liver and Novikoff hepatoma. 430 99


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